The HCV protease inhibitor compound of the formula XXIIb has entered clinical development.
The key step in the synthesis of the macrocyclic compounds of formula XXII is a ring closing metathesis (RCM) reaction of a diene compound in the presence of a suitable ring closing metathesis catalyst.
PCT Publication WO 2005/037214 and PCT Publication WO 2007/015824 disclose the RCM of a diene compound of the formula 2a in the presence of a Nolan or Hoveyda catalyst to afford the macrocyclic ester of formula 2b.

The prior art teaches acylation of the hydroxy group in a subsequent step. The RCM as disclosed in the art is unsatisfactory due to modest yields, low catalyst selectivity and the need to run the reaction with very low substrate concentrations resulting in low efficiency and high costs.